Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease.
We postulated that activation of a genetic program that tonically inhibits intimal cell death is a necessary condition for the pathogenesis of vascular disease. Studies of vascular lesions in humans and animal models documented increased expression of the anti-apoptotic gene product Bcl-xL within intimal cells. Downregulation of intimal cell bcl-xL expression with the use of antisense oligonucleotides induced apoptosis and acute regression of vascular lesions. These findings indicate that apoptosis regulatory genes such as bcl-xL are critical determinants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.
Pollman
M J
MJ
Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University, California 94305-5246, USA.
Hall
J L
JL
Mann
M J
MJ
Zhang
L
L
Gibbons
G H
GH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics*; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014652:Vascular Diseases / Q000473:pathology*; D051020:bcl-X Protein
D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein